The present invention relates to an oral dental preparation for the prevention of dental caries and periodontal diseases and, more particularly, to modified plaque-dispersing enzymes having lengthened activity in oral environments.
During recent years, it has been found that the organisms often associated with the formation of dental caries are certain streptococci belonging to the Streptococcus mutans group which contribute to the build-up of plaque and have been implicated in the development of dental caries and periodontal diseases. Specific strains of Streptococcus mutans can synthesize adhesive glucans which facilitate adherence of the organisms to tooth surfaces and contribute to the build-up of plaque. The significance of such glucans in relation to dental disease has been demonstrated through various investigations with "glucan synthesis-defective" mutants which have exhibited only low levels of virulence in animal experiments. Other streptococcal strains are additionally thought to synthesize fructan (levan) polysaccharides. Still other Actinomyces strains are major constituents of dental plaque and can be related to both root surface caries and periodontal disease. Such organisms also contribute to the formation of plaque through the synthesis of slimy, extracellular and cell-surface polysaccharides.
The extracellular streptococcal glucans are composed of glucosyl units linked in .alpha. 1,3 and .alpha. 1,6 configurations. Past attempts to control dental plaque formation with plaque-dispersing glucanohydrolases such as dextranase which hydrolyze 1,6-glucosyl linkages have had only limited success because the dextranase enzymes only partially degrade the glucans while leaving a water-insoluble residue. Recent investigations, in fact, have shown that this residual material is composed primarily of 1,3-linked glycosyl units with relatively few 1,6 linkages. While sources of 1,3 glucanohydrolases have been reported, the same are presently not commercially available. In addition, while an enzyme called mutanase has been isolated and was believed to be a 1,3-glucanohydrolase, the same, in spite of recent success as an anticaries agent in animal experiments, has only proved to be partially effective even in combination with dextranase as a means of degrading the streptococcal polysaccharides.
Thus, while dextranase has been proposed to be an effective caries preventive agent useful in the removal of bacteria on dextran containing plaque, the same has not been as successful as envisioned. Enzymes such as commercially available Penicillium dextranase have insufficient time to degrade plaque polysaccharides to any significant extent when such enzymes are introduced to tooth surfaces by conventional mouthwash, toothpaste, etc., where normal salivary flow, gingival fluid, and dietary liquids tend to wash the tooth surfaces and remove or dilute water soluble components in contact with the tooth surface. Such clearance can be observed in a matter of minutes and is increased when salivary flow is stimulated by taste and chewing. In this regard, the pH of oral fluid has been found to vary from about 5.4 to 7.8 and to be mostly in the range of 6.2 to 7.4. Such oral fluids are found on the tooth enamel which is composed primarily of a form of calcium phosphate called hydroxyapatite. While dextranases will usually bind to hydroxyapatite at lower acidic pH, the retention of these enzymes may be diminished in the mouth by the coating of the teeth with proteins, mucins, or other organic films from saliva, dental plaque, etc., and by the tendency for the pH of the oral fluid to rise to the 6.2 to 7.4 range. Consequently, such enzymes have their best chance to contact the hydroxyapatite directly after the teeth have been cleaned.
Accordingly, the present invention has been developed to overcome the shortcomings of the above known and similar techniques and to provide modified plaque-dispersing enzymes for prolonged activity through improved adherence to enamel surfaces.